1. Field of the Invention
The present invention relates to a method for preparing .alpha.-(4-isobutylphenyl)propionic acid, its precursor, i.e., .alpha.-(4-isobutylphenyl)propionaldehyde, or an alkyl .alpha.-(4-isobutylphenyl)propionate at low cost and in high purity.
More specifically, the present invention relates to a method for preparing .alpha.-(4-isobutylphenyl)propionic acid or its precursor which comprises the steps of dehydrogenating p-isobutylethylbenzene to form p-isobutylstyrene, and carbonylating p-isobutylstyrene to form .alpha.-(4-isobutylphenyl)propionic acid or its precursor, i.e., .alpha.-(4-isobutylphenyl)propionaldehyde or an alkyl .alpha.-(4-isobutylphenyl)propionate.
Another method of the present invention contains the step of forming p-isobutylethylbenzene. That is, the second method of the present invention comprises the three steps of the step I of alkylating isobutylbenzene or 4-ethyltoluene with ethylene or propylene to from p-isobutylethylbenzene, the step II of dehydrogenating p-isobutylethylbenzene to form p-isobutylstyrene, and the step III of carbonylating p-isobutylstyrene to form .alpha.-(4-isobutylphenyl)propionic acid or its precursor, i.e., .alpha.-(4-isobutylphenyl)propionaldehyde or an alkyl .alpha.-(4-isobutylphenyl)propionate.
This .alpha.-(4-isobutylphenyl)propionic acid is a useful medicine (trade name Ibuprophen) having alleviation effects of fever and pain and antiphlogistic effect, as described in British Patent No. 971700, French Patent No. 1549758 and the like.
It is known that .alpha.-(4-isobutylphenyl)propionaldehyde obtained in the step III of the present invention can be easily converted into .alpha.-(4-isobutylphenyl)propionic acid by oxidization in a known manner. Similarly, the alkyl .alpha.-(4-isobutylphenyl)propionate can be easily converted into .alpha.-(4-isobutylphenyl)propionic acid by hydrolysis with an acid or an alkali in a known manner. Therefore, each of these compounds can be considered to be the precursor for the preparation of .alpha.-(4-isobutylphenyl)propionic acid.
2. Description of the Prior Art
Heretofore, .alpha.-(4-isobutylphenyl)propionic acid and its precursor have been synthesized from an extremely great number of compounds as starting materials by various methods.
However, in order to synthesize .alpha.-(4-isobutylphenyl)propionic acid and its precursor at low cost and in high purity, the following requirements are needful:
(a) Starting materials should be simple compounds.
(b) In a reaction to be utilized, an intermediate in the each step should also be as simple and stable as possible.
(c) In place of expensive reagents, inexpensive reagents or catalysts should be employed.
(d) The number of steps for the synthesis should be as few as possible.
(e) Since an isobutyl group is liable to bring about skeletal isomerization, it is necessary to use a reaction in which the isomerization and other undesirable phenomenons are inhibited as much as possible.
For example, in Japanese Patent Laid-open Publication No. 100042/1976 which suggests a synthetic method of a-(4-isobutylphenyl)propionaldehyde, a Grignard reagent of isobutylbenzene which is unstable and difficult to handle is used as the starting material, and a Lewis acid such as BF.sub.3 is also used. Therefore, the isobutyl group tends to isomerize. Furthermore, in Japanese Patent Laid-open Publication No. 82740/1978, a compound such as metallic lithium which is difficult to handle is utilized.
Additionally, in Japanese Patent Laid-open Publication No. 13351/1974 which discloses a method for the preparation of .alpha.-(4-isobutylphenyl)propionic acid, isobutylbenzene is used as the starting material, but aluminum chloride is used as a catalyst. Thus, the isobutyl group tends to isomerize. In addition, expensive reagents are used.
In methods described in French Patent No. 1549758 and British Patent No. 1160725, p-isobutylacetophenone is used as the starting material.
However, p-isobutylacetophenone is not considered to be an inexpensive compound for the undermentioned reason. The most economical synthesis of p-isobutylacetophenone is to use isobutylbenzene as the starting material, but it is not preferable from an economical viewpoint to convert isobutylbenzene into p-isobutylacetophenone. That is, for the sake of the conversion into p-isobutylacetophenone, it is indispensable to make use of acetyl chloride which is an expensive and unstable material, and in addition, anhydrous aluminum chloride which is very sensitive to water must be used as a reaction catalyst at least in an amount equimolar with acetyl chloride, i.e., in a large amount. For example, even if this conversion reaction proceeds stoichiometrically in a yield of 100%, anhydrous aluminum chloride as much as 700 kg must be used to manufacture 1 ton of p-isobutylacetophenone. Moreover, after the end of the reaction, 410 kg of aluminum hydroxide and 750 kg of a chlorine ion result from the inactivation of anhydrous aluminum chloride, and thus it is additionally necessary to treat 1,160 kg of wastes, the amount of which is much greater than that of the manufactured p-isobutylacetophenone, so as to make them harmless. For this reason, p-isobutylacetophenone as the starting material is expensive, and needless to say, the process using this starting material is expensive. Furthermore, the conversion of p-isobutylacetophenone into .alpha.-(4-isobutylphenyl)propionic acid proceeds intricate intermediates, and it is fair to say that known method is not always economical from an industrial viewpoint.
U.S. Pat. No. 4,694,100 suggests a method for preparing .alpha.-(4-isobutylphenyl)propionic acid from p-isobutylstyrene through a hydroformylation reaction or a Reppe reaction. This method is economically excellent, because p-isobutylstyrene which is the starting material is simple and stable, and because the hydroformylation reaction and the Reppe reaction do not require expensive reagents. However, in these conventional manufacturing methods using p-isobutylstyrene, a complex reaction route is taken or expensive reagents are employed, so that the above-mentioned advantages are lost.
Japanese Patent Laid-open Publication No. 24534/1986 discloses a method which comprises subjecting isobutylbenzene and acetaldehyde to condensation reaction in the presence of a sulfuric acid catalyst to form 1,1-bis(p-isobutylphenyl)ethane, catalystically decomposing the latter to p-isobutylstyrene by the use of an acid catalyst, reacting the resultant compound with carbon monoxide and hydrogen in the presence of a carbonylation complex catalyst in order to obtain .alpha.-(4-isobutylphenyl)propionaldehyde. However, since the above-mentioned method employs sulfuric acid, the sulfonation reaction of isobutylbenzene itself which is the valuable raw material cannot be avoided, so that a part of isobutylbenzene is lost as a sulfonated compound, which means that the method is economically unpreferable. In addition, since this condensation reaction is a dehydration reaction, sulfuric acid which is used as the catalyst is diluted with the resulting water, and thus in order to reuse the catalyst, the diluted sulfuric acid must be treated by, for example, high-temperature distillation, in which devices are liable to corrode. Additionally, a great deal of the sulfonated compound is dissolved in a sulfonic acid phase, and therefore the catalyst concentration cannot be easily recovered by the simple distillation. In consequence, the resultant water must be removed through chemical reaction by the use of anhydrous sulfuric acid or fuming sulfuric acid, with the result that the cost of the catalyst increases.
As discussed above, the conventional techniques regarding the manufacture of .alpha.-(4-isobutylphenyl)propionaldehyde are not considered to be economical, and the development of more convenient manufacturing methods is demanded.